Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

ObjectiveTo investigate the effect of Shouwuwan on the synaptic plasticity of hippocampal neurons in the rat model of D-galactose-induced aging via the mammalian target of rapamycin （mTOR） signaling pathway. MethodA total of 50 male SPF-grade SD rats were randomized into normal group， model group， vitamin E （0.018 g·kg^-1） group， and low- and high-dose （1.08，2.16 g·kg^-1， respectively） Shouwuwan groups. Except the normal group， the other four groups were treated with D-galactose （120 mg·kg^-1） for the modeling of aging. The rats were simultaneously administrated with corresponding agents by gavage. After six weeks of modeling， Morris water maze test was carried out to examine the behavioral changes. The whole brain and hippocampus samples were collected. The expression of postsynaptic density protein-95 （PSD-95） and synaptophysin （SYN） in the hippocampus was detected by immunohistochemistry. Golgi staining was employed to observe the changes in the morphology and function of neurons. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were respectively employed to determine the mRNA and protein levels of mTOR， phosphorylated （p）-mTOR， p70 ribosome protein S6 kinase （p70S6K）， phosphorylated （p）-p70S6K， eukaryotic translation initiation factor 4E-binding protein 2 （4EBP2）， and phosphorylated （p）-4EBP2 in the hippocampus. ResultCompared with the normal group， the model group showed slow swimming （P<0.01）， extended total swimming distance （P<0.05）， prolonged latency （P<0.01）， and decreased crossing number （P<0.01）. The modeling inhibited the expression of PSD-95 and SYN in the CA1 region of the hippocampus （P<0.01）， with the weakest staining effect and the smallest region， decreased the intersections of hippocampal neuron dendrites with concentric circles at the concentric distance of 100， 140， 180， and 200 μm from the cell body （P<0.01）， and reduced the length and density of dendritic spine （P<0.01）. In addition， the modeling up-regulated the mRNA levels of mTOR and p70S6K and the protein levels of p-mTOR and p-p70S6K （P<0.01） and down-regulated the mRNA level of 4EBP2 and the protein levels of 4EBP2 and p-4EBP2 （P<0.01）. Compared with the model group， low- and high-dose Shouwuwan increased the average swimming speed （P<0.01）， shortened the latency （P<0.01）， increased the crossing number （P<0.01）， promoted the expression of PSD-95 and SYN in the hippocampal CA1 region （P<0.01）， increased the intersections between hippocampal neuronal dendrites and concentric circles at the concentric distance of 100， 140， 180，200 μm from the cell body （P<0.01）， and increased the number， length， and density of dendritic spine （P<0.01）. Furthermore， Shouwuwan down-regulated the protein levels of p-mTOR and p-p70S6K （P<0.01）， up-regulated the protein levels of 4EBP2 and p-4EBP2 （P<0.05，P<0.01）， down-regulated the mRNA levels of mTOR and p70S6K （P<0.01）， and up-regulated the mRNA level of 4EBP2 （P<0.01）. ConclusionShouwuwan can improve the learning and memory ability of rats exposed to D-galactose， promote the expression of proteins associated with synaptic plasticity， improve the morphology of neurons， repair neural function， reduce neuronal apoptosis， and inhibit mTOR signaling pathway to delay brain aging.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

ObjectiveTo investigate the effect of Shouwuwan on apoptosis of hippocampal neurons in D-galactose-induced aging rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodFifty male SD rats of SPF grade were randomly divided into normal group， model group， vitamin E group， and Shouwuwan medium- and high-dose groups. Except the normal group， the other four groups were given D-galactose （120 mg·kg^-1） to prepare aging model. Additionally， Shouwuwan was used to intervene in the Shouwuwan medium- and high-dose groups （1.08 and 2.16 g·kg^-1， respectively）， and vitamin E group （0.018 g·kg^-1） was given vitamin E by gavage. After 6 weeks of modeling， the whole brain and hippocampal tissue were taken and the morphological changes of hippocampal neurons were observed by Nissl staining. The apoptosis of hippocampal cells was detected by in situ end labeling ［TdT-mediated dUTP nick-end labeling （TUNEL）］. The protein expression levels of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， Caspase-3， forkhead box protein O3a （FoxO3a）， p-FoxO3a， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected by Western blot. Real-time fluorescence quantitative PCR （Real-time PCR） was performed to determine the mRNA expression level of FoxO3a in hippocampus. ResultCompared with the conditions in the normal group， the apoptotic cells of hippocampal neurons in the model group were significantly increased， and the apoptosis index was elevated （P<0.01）. Nissl staining of the hippocampal CA1 region showed that hippocampal neurons were lost and sparse， and the number of Nissl bodies was reduced， with pyknosis and deep staining. The relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were all increased （P<0.01）， while the relative protein expression of FoxO3a， p-FoxO3a and Bcl-2， and p-FoxO3a/FoxO3a ratio were decreased （P<0.01）. The mRNA expression of FoxO3a was lowered （P<0.01）. Compared with the conditions in the model group， after treatment with Shouwuwan， the apoptotic cells were markedly reduced， and the apoptosis index of each treatment group was decreased （P<0.01）. Nissl staining of the hippocampal CA1 region demonstrated that the loss of neurons in each treatment group was improved， and Nissl bodies were increased and densely arranged. There was no statistically significant difference in the relative protein expression of PI3K and Akt in each group. In Shouwuwan medium- and high-dose groups， the relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were decreased， while the relative protein expression of FoxO3a andp-FoxO3a， and Bcl-2， and p-FoxO3a/FoxO3a ratio were increased （P<0.01）. The mRNA expression of FoxO3a was up-regulated （P<0.01）. ConclusionShouwuwan could improve the structure of hippocampal neurons， inhibit PI3K/Akt signal pathway， down-regulate Caspase-3 and Bax， activate FoxO3a， and up-regulate Bcl-2 and Bcl-2/Bax ratio， to reduce neuronal apoptosis.

Objective To investigate the prevalence of metabolic syndrome (MS) among adults in rural areas of Ningxia Hui autonomous region.Methods A cross-sectional study was conducted in 10 639 adults enrolled with a multistage method from Jingyuan County.The MS was identified according to Chinese type 2 diabetes prevention guide (2013).Results Among all the subjects, 17.4% of them met the MS definition with the standardized prevalence of 14.7% after adjustment of sex and age.The prevalence and standardized rate of MS in men were 19.9% and 17.3%, and in women were 15.3% and 13.5%.The prevalence of MS in men was higher than that in women(P<0.001) and increased with aging in both genders.The prevalence and standardized rate of abdominal obesity,hyperglycemia,hypertension,high triglycerides,and low HDL-C were 19.5% and 16.7%, 15.0% and 12.9%, 42.0% and 37.1%, 25.8% and 23.1%, 28.5% and 27.7%,respectively.The rate of abdominal obesity was higher in women than in men (20.5% vs 18.2%, P=0.004), whereas the rate of hypertension, high triglycerides, and low HDL-C were higher in men than in women (all P<0.01).The prevalence of having one parameter of the MS was 68.4%.Conclusion The prevalence of MS is higher in rural areas of Ningxia Hui autonomous region, suggesting that a series of comprehensive prevention measures should be carried out to prevent and control the MS so as to improve the public health conditions in rural areas.

Objective To observe the effect of electroacupuncture at Baihui (GV20) and Shenting (GV24) on learning-memory function and ultrastructure in hippocampal CA1 region of rats after cerebral ischmeia-reperfusion. Methods A total of 25 male Sprague-Dawley rats were randomly divided into sham group (n=6) and operation group (n=19). The operation group was occluded the left middle cerebral arter-ies with modified Longa's methods for 90 minutes and reperfused, and twelve qualified rats of them were randomly divided into model group (n=6) and electroacupuncture group (n=6), the later accepted electroacupuncture at Baihui and Shenting for seven days. They were as-sessed with Longa's scores, and tested with Barnes maze. Their cerebral infarct volume was tested with magnetic resonance imaging T2-weighted image. The ultrastructure of synapse in hippocampal CA1 region was observed with transmission electron microscope. Results Compared with the model group, the Longa's score improved (P<0.05), the infarct volume decreased (P<0.01), the average escape latency decreased (P<0.01) and the times entering the wrong hole decreased (P<0.001) in the electroacupuncture group. Under the transmission elec-tron microscope, the number of synapse decreased in the model group, with the structure damage and vesicles sparse;compared with the model group, the number of synapse increased in the electroacupuncture group, with clear and complete structure and rich vesicles. Conclu-sion Electroacupuncture at Baihui and Shenting can improve the learning-memory function in rats after cerebral ischmeia-reperfusion, which may relate to improvement of synaptic plasticity and ameliorating ultrastructure in hippocampal CA1 region.

Humans ; Liver Cirrhosis ; Renin-Angiotensin System ; Self-Control

Objective: To study clinical application value of dobutamine stress echocardiography (DSE) and nitroglycerin stress single photon emission computed tomography (SPECT) for evaluation of restenosis after percutaneous coronary intervention (PCI). Methods: A total of 39 patients after PCI were examined by DSE and SPECT one week before coronary angiography (CAG). Dose incremental program of dobutamine included five levels：5μg•kg-1•min-1, 10μg• kg-1• min-1, 20μg•kg-1•min-1, 30μg•kg-1•min-1, 40μg•kg-1•min-1, and each level maintained for three minutes. Sensitivity, specificity and accuracy of DSE and SPECT were determined according to CAG examined result and examined results were compared between DSE and SPECT. Results: Compared with CAG, SPECT and DSE were no significant differences （P>0.05）in sensitivity (83.3% vs. 75.0%) and accuracy (71.8% vs. 87.2%) for evaluating restenosis after PCI, but compared with SPECT, DSE possessed higher specificity (66.7% vs. 92.6%). Conclusions: Dobutamine stress echocardiography is accurate, and its specificity is better than that of SPECT for evaluating restenosis after percutaneous coronary intervention.

Multifunctional proteglycan, versican, is recently recognized as a gene related to tumor metastasis. Versican may maintain or inhibit cell growth, affect cell adherence and regulate the mutual interaction between cells or cell and matrix. Higher expression of versican always correlates with worse prognosis.

Objective Using transcranial Doppler (TCD) to evaluate the effect of selective shunt (SS) during carotid endarterectomy (CEA). Methods TCD was used for intraoperative bilateral middle cerebral artery (MCA) cerebral blood flow continuous monitoring in 169 patients with carotid stenosis treated with CEA. The patients were divided into shunt (n =32)and non-shunt (n = 137) groups according to whether they performed shunt or not. The open approaches of anterior collateral circulation were recorded. The peak systolic velocity (PSV),mean velocity (MV), pulsatility index (PI), and ratio of MV in bilateral MCA were compared after anesthesia, before and after carotid artery occlusion, before and after shunt, and after carotid artery open. Results MV before carotid artery occlusion in the shunt and non-shunt groups were 34.73 ± 13.54 cm/sand 35.32 ± 13.18 cm/s, respectively, and there was no significant difference (P = 0. 825). MV in the shunt group after carotid artery occlusion was significantly decreased in the non-shunt group (P =0. 000). The mean decline rate of MCA MV was 69.34% ± 20. 93%, and it was decreased more significantly than that in the non-shunt group (P=0. 000). The decline rate of MCA MV was increased significantly after shunt operation, the average increase was 35.68 ± 16.69 cm/s (P=0. 000). Conclusions TCD can objectively evaluate the hemodynamic changes before and after shunt operation.